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Updated: Oct 26, 2025
Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone
Jinhan Nam1, Tapani K Koppinen1, Merja H Voutilainen1
1Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Abstract:
Multiple sclerosis (MS) is a progressive autoimmune disease characterized by T-cell mediated demyelination in central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a widely used in vivo disease model of MS. Glucocorticoids such as dexamethasone (dex) function as immunosuppressants and are commonly used to treat acute exacerbations of MS. Dex is also often used as a positive control in EAE studies, as it has been shown to promote motor behavior, inhibit immune cell infiltration into the CNS and regulate the activation of glial cell in EAE. This study further validated the effects of intravenously administrated dex by time-dependent fashion in EAE. Dex postponed clinical signs and motor defects in early stages of EAE. Histological analysis revealed that the degeneration of myelin and axons, as well as the infiltration of peripheral immune cells into the white matter of spinal cord was inhibited by dex in early stages of EAE. Additionally, dex-treatment delayed the neuroinflammatory activation of microglia and astrocytes. Furthermore, this study analyzed the expression of the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in EAE, and the effect of treatment with dex on MANF-expression. We show that in dex-treated EAE mice expression MANF increased within myelinated areas of spinal cord white matter. We also show that intravenous administration with hMANF in EAE mice improved clinical signs and motor behavior in the early stage of EAE. Our report gives insight to the progression of EAE by providing a time-dependent analysis. Moreover, this study investigates the link between MANF and the EAE model, and shows that MANF is a potential drug candidate for MS.
Insights
Dexamethasone (dex) treatment in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model, delayed disease onset and reduced inflammation. Human mesencephalic astrocyte-derived neurotrophic factor (hMANF) also improved clinical signs, suggesting its therapeutic potential for MS.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a T-cell mediated autoimmune demyelinating disease of the central nervous system (CNS).
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS pathogenesis and therapeutic strategies.
- Dexamethasone (dex), a glucocorticoid, is a standard treatment for MS exacerbations and a common positive control in EAE studies.
Purpose of the Study:
- To investigate the time-dependent effects of intravenous dexamethasone administration in the EAE model.
- To analyze the impact of dexamethasone on neuroinflammation and myelin/axonal integrity in EAE.
- To explore the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in EAE and its modulation by dexamethasone.
Main Methods:
- Induction of EAE in mice and time-dependent administration of dexamethasone.
- Assessment of clinical signs and motor behavior.
- Histological analysis of spinal cord tissue to evaluate demyelination, axonal damage, and immune cell infiltration.
- Analysis of glial cell activation (microglia and astrocytes).
- Measurement of MANF expression in dexamethasone-treated EAE mice.
- Intravenous administration of hMANF in EAE mice.
Main Results:
- Dexamethasone treatment significantly postponed clinical symptoms and motor deficits in the early stages of EAE.
- Histological examination showed that dexamethasone inhibited myelin and axonal degeneration and reduced peripheral immune cell infiltration into the spinal cord white matter.
- Dexamethasone delayed the neuroinflammatory activation of microglia and astrocytes.
- MANF expression was upregulated in the spinal cord white matter of dexamethasone-treated EAE mice.
- Intravenous administration of hMANF ameliorated clinical signs and motor behavior in the early phase of EAE.
Conclusions:
- Dexamethasone exhibits neuroprotective and anti-inflammatory effects in the EAE model, with benefits observed in a time-dependent manner.
- MANF expression is increased by dexamethasone treatment in EAE, and exogenous hMANF demonstrates therapeutic potential.
- MANF represents a promising therapeutic candidate for multiple sclerosis, warranting further investigation.
